In our Phase I trial of recombinant leukocyte interferon (1981-82) in patients with a variety of disseminated cancers, we demonstrated that this agent could be administered up to doses of 50 x 50 million/meter 2 i.m. 3 times weekly without unacceptable toxicity. This trial also showed objective evidence of antitumor response (partial remissions) in some patients with non-Hodgkin's lymphoma, breast cancer, chronic lymphocytic leukemia and Hodgkin's disease. We decided to initiate a Phase II efficacy trial of recombinant leukocyte interferon at a maximum tolerated dose, with dose reductions as necessary for unacceptable toxicity. Phase II efficacy trials were initiated in patients with various lymphoproliferative disorders, including non-Hodgkin's lymphoma, chronic lymphocytic leukemia and cutaneous T-cell lymphoma, as well as patients with refractory metastatic breast cancer. Eighteen patients with metastatic breast cancer were treated in 1982 with recombinant leukocyte A interferon, with 16 patients progressing while on therapy and 2 remaining stable. Eighty-four patients with a variety of lymphomas have been treated, with a 56% response rate in 24 patients with favorable-histology lymphoma (9 partial responses, 5 complete responses) and a 45% response rate in 20 patients with cutaneous T-cell lymphoma (9 partial responses). Only 2 of 19 patients with chronic lymphocytic leukemia and 3 of 16 patients with unfavorable-histology lymphoma responsed. Our currently active studies include randomizing favorable-histology lymphoma patients to low-dose daily recombinant interferon-Alpha (3 million) versus 60 million twice per week to see if the well tolerated low-dose regimen is as efficacious as the high dose schedule. We are also treating patients with hairy cell leukemia with daily doses of recombinant interferon-Alpha (3 million with excellent clinical results (13 responses among our first 14 patients).